The safety and efficacy of ketamine NMDA receptor blocker as a therapeutic intervention for PTSD review of a randomized clinical trial

Behav Brain Res. 2022 Apr 29:424:113804. doi: 10.1016/j.bbr.2022.113804. Epub 2022 Feb 16.


Objective: Posttraumatic stress disorder (PTSD) has long-lasting debilitating symptoms. PTSD causes a significant burden on healthcare workers and victims' families. The US Food Drug Administration (FDA) has approved only two Serotonin Selective Reuptake Inhibitors (SSRI), sertraline, and paroxetine as pharmacological interventions for PTSD. SSRI has a 50-60% response rate and up to 30% remission rate with a high relapse rate. Ketamine is an NMDA receptor blocker, has a rapid effective onset, a potent antidepressant with anti-suicidal, neuroprotective, and cognitive-enhancement properties.

Method: We retrieved randomized clinical trials (RCT) on PubMed, PubMed Central, and Medline Database of clinical trial studies until Jan/2022. We used the following keywords: "posttraumatic stress disorder. "AND "Ketamine." AND "Esketamine" AND "NMDA receptor antagonist" AND "treatment, pharmacological intervention, management. ". We used Medical Subject Heading [Mesh] Term for "ketamine" and "Esketamine" And "Receptors, N-Methyl-D-Aspartate" and "Stress Disorders, Post-Traumatic" and "Disease management.".

Result: All qualified five randomized clinical studies showed rapid and clear benefits of Ketamine infusion for PTSD symptoms resistant to conventional medications. The clinical improvements were evident in three of the four PTSD symptom categories, intrusions, avoidance, and negative alterations in cognitions and mood. In addition, Ketamine administration was safe well-tolerated, with transient dissociation as the main side effect reported. Ketamine infusion also positively affects comorbidities like chronic pain, alcohol use disorder, and major depression.

Conclusion: Ketamine showed fast, safe, highly effective pharmaceutical intervention for chronic PTSD symptoms. No correlation between ketamine potency and patient age, sex and/or body mass index. Further studies are needed to understand the appropriate therapeutic dose, onset, route of administration, duration of the treatment and comorbidity benefit.

Keywords: Ketamine; NMDA receptor; Post-traumatic stress disorder; Treatment.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / adverse effects
  • Humans
  • Ketamine* / adverse effects
  • Randomized Controlled Trials as Topic
  • Receptors, N-Methyl-D-Aspartate* / antagonists & inhibitors
  • Stress Disorders, Post-Traumatic* / drug therapy
  • Treatment Outcome


  • Antidepressive Agents
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine